The allosteric interaction of otenzepad (AF-DX 116) at muscarinic M2 receptors in guinea pig atria

European Journal of Pharmacology
A LanzafameF Mitchelson

Abstract

The effects of the muscarinic receptor antagonist, otenzepad, in combination with the competitive antagonists N-methylscopolamine, dexetimide and atropine, or the allosteric modulators, C(7)/3'-phth, gallamine and alcuronium, were measured in the guinea pig electrically driven left atrium using the agonists, carbachol or acetylcholine. Otenzepad, in combination with C(7)/3'-phth or gallamine, gave concentration-ratios close to additive and in agreement with theoretical model predictions for combination of two allosteric modulators acting at a common site. However, when otenzepad was combined with alcuronium, dexetimide or N-methylscopolamine, supra-additive effects were observed. For either competitive antagonist in combination with otenzepad, the degree of supra-additivity was more evident after 2-h equilibration than after 40 min. When otenzepad was combined with atropine, no supra-additivity was observed with carbachol as the agonist, but was evident with acetylcholine. Otenzepad was also unable to fully inhibit [3H]N-methylscopolamine binding when the radioligand was employed at a concentration of approximately 100 x K(D). It is concluded that the action of otenzepad involves an allosteric site and a number of possibilities...Continue Reading

References

Nov 1, 1976·British Journal of Pharmacology·A L Clark, F Mitchelson
Apr 10, 1990·European Journal of Pharmacology·N H Lee, E E el-Fakahany
Jan 1, 1989·Life Sciences·H F PitschnerA Wellstein
Mar 1, 1988·British Journal of Pharmacology·E L KunyszR L Whiting
May 5, 1986·Life Sciences·A GiachettiE Montagna
Jun 1, 1993·Pharmacology & Therapeutics·M P Caulfield
Jun 1, 1995·Trends in Pharmacological Sciences·S Tucek, J Proska
Nov 28, 1996·European Journal of Pharmacology·A LanzafameF Mitchelson
Aug 24, 1965·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·W D PATON, H P RANG

Related Concepts

AFDX 116
heptane-1,7-bis-(dimethyl-3'-phthalimidopropyl)ammonium bromide
Acetilcolina Cusi
Allosteric Regulation
Quaternary Ammonium Compounds
Metazoa
Atropine Sulfate Anhydrous
Carboptic
Cardiotonic Agents
Spasmentral

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